Regenerative medicine, in which a body part or organ which has been rendered dysfunctional due to various diseases or traumatic injuries is replaced with a regenerated body part or organ, is showing promise as a next-generation medical technique to complement medical transplantation (Non-Patent Literature 1). In past research of regenerative medicine, advances have been made in stem cell transplantation therapy in which stem cells or precursor cells are transplanted into an injured tissue or a partially dysfunctional organ to restore its function.
In regeneration of two-dimensional tissue consisting of a single type of cell, a tissue regeneration technology in which skin or corneal epithelial cells, cardiac muscle cells, and the like are organized by culturing the cells in a sheet form using cell sheet technology is nearing practical application. Therein, it is now possible to regenerate functional skin tissue by stratifying fibroblasts, which are mesenchymal cells, and skin epidermal cells to artificially reproduce a histologically-appropriate layer structure, and this technique has been clinically applied in the treatment of severe burns.
Meanwhile, it is known that in an organ, multiple types of functional cells take on a three-dimensional arrangement to express a unique function. Almost all organs are generated by interactions between epithelial cells and mesenchymal cells during the fetal period, and exhibit unique morphology and organ functions. In current regenerative medicine techniques, it is difficult to arrange multiple types of cells in a three-dimensional fashion, and a regenerative organ construct that can immediately function ex vivo has yet to be developed.
Recently, research is being conducted with the goal of organ regeneration by regenerating an organ germ and reproducing its developmental process for epithelial appendages such as teeth and salivary glands and skin appendages such as hair follicles. These organs are not directly related to the maintenance of life, but they are known to fall into organ loss or dysfunction. As an example, mention may be made of tooth loss due to dental caries, injury, and tooth germ hypoplasia, salivary secretion disorder associated with aging, and hair loss due to male pattern baldness and hair follicular dysplasia. These kinds of organ loss or dysfunction have a large impact on QOL (quality of life), and thus high expectations have been placed on functional restoration by organ regeneration. Particularly, in tooth regeneration, regeneration of a functional tooth having all of the physiological functions of a tooth has been demonstrated by transplantation of regenerative tooth germ in which epithelial cells derived from embryonic tooth germ and mesenchymal cells derived from embryonic tooth germ are appropriately arranged in a three-dimensional fashion, transplantation of a regenerative tooth unit that was ectopically regenerated in vivo, and transplantation of a functional unit containing a tooth, alveolar bone, and periodontal membrane (for example, refer to Patent Literature 1). Further, it has also been demonstrated that regenerative tooth germ or a regenerative tooth unit having similarly characteristic cell arrangement and directionality can be obtained when using oral cavity epithelial cells or primary cultured cells thereof as the epithelial cells (for example, refer to Patent Literature 2), when using amnion-derived cells as the mesenchymal cells (for example, refer to Patent Literature 3), and when using cells obtained by differentiation induction of totipotent stem cells as the mesenchymal cells (for example, refer to Patent Literature 4).
From these research results, it can be said that the feasibility of functional organ regeneration by transplantation of a regenerative organ germ or an organ regenerated from a regenerative organ germ has been demonstrated, and organ replacement and regenerative medical techniques using regenerative organ primordia are now sought for other epithelial appendages.